Efficacy of alirocumab in high cardiovascular risk populations with or without heterozygous familial hypercholesterolemia: Pooled analysis of eight ODYSSEY.

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Efficacy of alirocumab in high cardiovascular risk populations with or without heterozygous familial hypercholesterolemia: Pooled analysis of eight ODYSSEY Phase 3 clinical program trials Michel Farnier, Daniel Gaudet, Velichka Valcheva, Pascal Minini, Kathryn Miller, Bertrand Cariou International Journal of Cardiology Volume 223, Pages 750-757 (November 2016) DOI: 10.1016/j.ijcard.2016.08.273 Copyright © 2016 The Authors Terms and Conditions

Fig. 1 Pooling strategy. For purposes of this analysis, efficacy data were analyzed in three pools according to alirocumab dose (75/150mg or 150mg Q2W) and control (ezetimibe or placebo). For safety analysis, Pool 2 and Pool 3 were combined. n values refer to the number of patients in the randomized study populations. a Maximally tolerated statin was defined as atorvastatin 40–80mg, rosuvastatin 20–40mg, or simvastatin 80mg. Fixed doses of atorvastatin 20–40mg and rosuvastatin 10–20mg were used in OPTIONS I and II, respectively. b In the OPTIONS studies, dose was increased if LDL-C was ≥70mg/dL (prior CHD) or ≥100mg/dL (CHD risk equivalents). CHD, coronary heart disease; HeFH, heterozygous familial hypercholesterolemia; FH, familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering therapy; Q2W, every 2weeks. Clinicaltrials.gov identifiers: COMBO II, NCT01644188; OPTIONS I, NCT01730040; OPTIONS II, NCT01730053; FH I, NCT01623115; FH II, NCT01709500; COMBO I, NCT01644175; LONG TERM, NCT01507831; HIGH FH, NCT01617655. International Journal of Cardiology 2016 223, 750-757DOI: (10.1016/j.ijcard.2016.08.273) Copyright © 2016 The Authors Terms and Conditions

Fig. 2 LDL-C percentage reductions from baseline to Weeks 12 (a) and 24 (b)a. * p<0.0001 vs. control. a Intention-to-treat analysis, including all lipid data collected regardless of adherence to treatment. b Dose increased from 75 to 150mg Q2W at Week 12 in 18% and 35% of patients in the ezetimibe- and placebo-controlled pools, respectively. ALI, alirocumab; EZE, ezetimibe, LDL-C, low-density lipoprotein cholesterol; LS, least squares; PBO, placebo; Q2W, every 2weeks; SE standard error. International Journal of Cardiology 2016 223, 750-757DOI: (10.1016/j.ijcard.2016.08.273) Copyright © 2016 The Authors Terms and Conditions

Fig. 3 LDL-C change over time (on-treatment population) (a) Pool 1; (b) Pool 2; (C) Pool 3.a * All p values <0.0001 vs. control. (aPool 1 COMBO II to Week 104, OPTIONS I and OPTIONS II not included due to shorter duration (Week 24); Pool 2 FH I and FH II to Week 78, COMBO I not included due to shorter duration (52weeks); Pool 3 LONG TERM and, HIGH FH, both studies shown to Week 78.). LDL-C, low-density lipoprotein cholesterol; LS, least squares; SE standard error. International Journal of Cardiology 2016 223, 750-757DOI: (10.1016/j.ijcard.2016.08.273) Copyright © 2016 The Authors Terms and Conditions

Fig. 4 Achievement of risk-based LDL-C goalsa at Week 12 (a) and 24 (b)b. * p<0.0001 vs. control. a LDL-C goals were <70mg/dL for patients at very high CV risk, and <100mg/dL for patients with high CV risk. Very high CV risk was defined as patients with CHD or CHD risk equivalents. High CV risk was defined as all other patients in these studies. b intention-to-treat analysis. ALI, alirocumab; CHD, coronary heart disease; CV, cardiovascular; EZE, ezetimibe, LDL-C, low-density lipoprotein cholesterol; PBO, placebo. International Journal of Cardiology 2016 223, 750-757DOI: (10.1016/j.ijcard.2016.08.273) Copyright © 2016 The Authors Terms and Conditions

Fig. 5 Percentage changes in non-HDL-C, apo B, and Lp(a), at Week 12 (A, C, and E, respectively) and Week 24 (B, D, and F, respectively)a. * p<0.0001 vs. control. a Intention-to-treat analysis. Apo, apolipoprotein; ALI, alirocumab; EZE, ezetimibe, HDL-C, high-density lipoprotein cholesterol; Lp(a), lipoprotein (a); LS, least squares; PBO, placebo; SE, standard. International Journal of Cardiology 2016 223, 750-757DOI: (10.1016/j.ijcard.2016.08.273) Copyright © 2016 The Authors Terms and Conditions